'Designer' enzymes to boost hi-tech manufacturing

In nature, all life depends on one simple thing: the ability of organisms to carry out a ceaseless flow of highly varied and specialised chemical reactions. At the heart of all these reactions sits nature’s ‘secret weapon’ - enzymes. These are proteins which act as catalysts, allowing the reactions to take place at a rate which is simply unachievable with ‘classical’ chemical methods.

In modern industries like pharmaceuticals, food and agricultural science, key manufacturing processes depend on the same type of chemical reactions to those which occur in living organisms. The difference, unfortunately, is that for these reactions the immense catalysing power of enzymes is not available. The enzymes don’t exist. Or if they do, they are not available on a scale suitable for industrial use.

If such enzymes could somehow be engineered, they could transform the efficiency and performance of many industries and open up the prospect of a range of new products hitherto impossible to produce on any significant scale.

This task - finding a way to engineer nature’s enzymes to create new ‘designer’ enzymes, able to meet the needs of specific industrial processes – was the mission of OXYGREEN, a five-year European research project supported by 5.5 million euros of funding from the European Commission (EC). Starting work in 2008, the project brought together 12 partners including universities, research institutes and commercial enterprises from The Netherlands, Germany, Austria, Italy, France and Poland.

Specifically, the consortium focused on enzymes that use oxygen to carry out reactions, since these are among the most widely used and relevant chemical reactions for industry.

Importantly, the benefits of engineering these new ‘oxidative’ enzymes could extend well beyond the specific industries concerned. They could also have an important ‘green’ impact – hence the project’s name. Until now, oxidation processes used in industry, based on the use of chemical as opposed to biological catalysts, have typically been energy-intensive and environmentally unfriendly, using toxic materials such as heavy metals, producing unwanted by-products and resulting in major waste and recycling issues.

The beauty of enzymes is that these natural catalysts target only very specific molecules, meaning that they produce no or very few by-products. And being natural bio-catalysts they are of course biodegradable.

Drawing on a wide-range of expertise in fields including biochemistry, genetics, microbiology, chemistry and biotechnology, the OXYGREEN project was able to generate unprecedented understanding of the way in which oxidative enzymes function at an atom-by-atom level – even producing a ‘movie’ of the catalytic process which can now be viewed on the internet. The next objective was to explore ways of modifying, or engineering, those natural enzymes which appeared of most interest for their potential applicability in industrial processes.

Making use of the enzyme-modifying techniques pioneered by OXYGREEN, a number of promising results have already been achieved. A modified enzyme that can be used in the synthesis of a pharmaceutical has been identified and is currently being evaluated to see if it is good enough for industrial use. The same is true of a group of enzymes that can be used in synthesising a flavour compound for the food industry. Meanwhile, even more progress has been made with a modified enzyme for the production of a vitamin, with a patent application now filed.

There is no doubt that the engineering of new ‘designer’ enzymes is a key technology in a world where cleaner, cheaper and safer industrial processes are urgently needed. The groundbreaking work of OXYGREEN represents a giant step forward in enabling industry to harness the hidden power of nature to achieve precisely this goal.